Environmental exposures may increase risk for cancer and non-cancer chronic diseases, especially among susceptible subgroups of the population. Data from completed case-control studies of risk factors for adult leukemia and kidney disease are being analyzed. Both studies included hopsital patients and population based controls. The leukemia study was conducted in connection with Cancer and Leukemia Group B, a cooperative cancer treatment group, and allowed for interviewing patients immediately following diagnosis. Other studies include risk fctors for neurodegenerative diseases as well as a study of neurobehavioral effects of pesticides. A new project was initiated to follow up on results from the leukemia case-control study. In collaboration with investigators from the karolinska Institute, we are taking advantage of the existince of linkable registries on family groupings and cancer incidence to further explore the link between family cancer history and lrisk for leukemia. Few studies have evaluated the possible risk for adult leukemia associated with a family cancer history. Such a link can provide the impetus for further studies of specific genes and modes of inheritance. Since family history of cancer is a composite variable representing shared genes as well as exposures, family history may identify individuals with increased susceptibility due to increased likelihood of having one or more of several gene polymorphisms that are involved in cancer etiology. Cases and controls in the leukemia study provided information on cancer incidence and mortality in enumerated first and second-degree relatives and on their own exposure to known and suspected risk factors for leukemia. Relatives reported to have died since the advent of the National Death Index (NDI) were linked with that database in an attempt to validate cause of death. For those reported to have died prior to the NDI or for whom NDI matches were not found, death certificates were requested from individual states. We attempted to validate reports of cancer in family members and assess the quality of such data and reported on the ability of participants to accurately report such information. We previously reported suggestive evidence for an association between a family history of any cancer, hematopoietic cancer, leukemia, and breast and increased leukemia risk. We also found that persons with both a family history of breast cancer and one of several environmental risk factors (smoking, solvents, radiation) are at greater risk for leukemia than those with either one of these risk factors. In fact, for each of the exposures examined, increased risk for leukemia was observed only among persons with a family history of breast cancer. Family history of breast cancer may be a marker of susceptibility to a range of leukemia risk factors whose effects are generally weak or non-existent when considered alone. Linked population, family, and cancer registry data from Sweden are now being used to evaluate the association between breast cancer and leukemia in an independent dataset. We are linking data from the population-based cancer registry with the Swedish Family Register to compare risk of breast, leukemia and other cancer in the first degree relatives of leukemia patients. We are also evaluating the risk of leukemia among relatives of patients with breast cancer. The analysis of the possible link between leukemia and family history of breast cancer will be based on more than 18,000 leukemia probands and 32,000 female first degree relatives, among whom 766 have had breast cancer. For the counter analysis of leukemia risk in families with breast cancer, there are more than 114,000 probands with breast cancer and 757 relatives who were diagnosed with leukemia. The our analysis of leukemia risk associated with family history of leukemia will be based on 22,500 probalnds and 169 relatives with leukemia. This year we published a paper on leukemia risk associated with occupational exposures. We found that employment in occupations with potential for exposure to petroleum products was associated with increased risk for acute myeloid leukemia. Specifically, risks were increased with work in petroleum manufacturing, automobile manufacturing, or as a gas station attendant. Results were strengthened by significant dose-response trends and consistency with prior literature. We also found an association with work as a hairdresser which is consistent with our previously reported results on personal use of hair dyes. Additional analyses focusing on specific solvents and other chemical exposures and on use of medications are underway. The anaysis of data from the kidney disease study focused on beverage consumption in relation to risk. The incidence of treated end stage kidney disease has increased steadily in the US as as consumption of carbonated beverages which have been linked to kidney stones, which in turn may increase risk of chronic kidney disease. Such beverages may also have direct effects on kideny function that might lead to increased risk for kidney disease. Our study included 548 cases with renal disfunction confirmed by hospital chart review and 514 matched population controls. We found that consumption of heavy amounts of cola beverages appears to be associated with risk for kidney disease. This result was not explained by caffeine or use of artificial sweeteners and appears to be independent of effects of glucose consumption on risk for diabetes. A paper describing these results was submitted for publication.